Regulation of Antiarrhythmic Drug Propafenone Effects on the C-type KV1.4 Potassium Channel by PHo and K+.
10.3346/jkms.2009.24.1.84
- Author:
Zhiquan WANG
1
;
Shimin WANG
;
Jianjun LI
;
Xuejun JIANG
;
Neng WANG
Author Information
1. Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China. wangzhiquan1031@yahoo.com.cn
- Publication Type:Original Article
- Keywords:
Potassium Channels;
Anti-arrhythmic drug;
Ion Channels, Voltage-Gated;
Voltage Clamp;
Membrane Currents
- MeSH:
Animals;
Anti-Arrhythmia Agents/*pharmacology;
Hydrogen-Ion Concentration;
Inhibitory Concentration 50;
Kv1.4 Potassium Channel/*antagonists & inhibitors/metabolism;
Oocytes/drug effects/metabolism;
Patch-Clamp Techniques;
Potassium/*metabolism;
Potassium Channel Blockers/*pharmacology;
Propafenone/*pharmacology;
Xenopus laevis
- From:Journal of Korean Medical Science
2009;24(1):84-91
- CountryRepublic of Korea
- Language:English
-
Abstract:
The effects of the antiarrhythmic drug propafenone at c-type kv1.4 channels in Xenopus laevis oocytes were studied with the two-electrode voltage-clamp techinique. Defolliculated oocytes (stage V-VI) were injected with transcribed cRNAs of ferret Kv1.4 delta N channels. During recording, oocytes were continuously perfused with control solution or propafenone. Propafenone decreased the currents during voltage steps. The block was voltage-, use-, and concentration- dependent manners. The block was increased with positive going potentials. The voltage dependence of block could be fitted with the sum of monoexponential and a linear function. Propafenone accelerated the inactivate of current during the voltage step. The concentration of half-maximal block (IC(50)) was 121 micrometer/L. With high, normal, and low extracellular potassium concentrations, the changes of IC(50) value had no significant statistical differences. The block of propafenone was PH- dependent in high-, normal- and low- extracellular potassium concentrations. Acidification of the extracellular solution to PH 6.0 increased the IC50 values to 463 micrometer/L, alkalization to PH 8.0 reduced it to 58 micrometer/L. The results suggest that propafenone blocks the kv1.4 delta N channel in the open state and give some hints for an intracellular site of action.
